Alzheimer’s Redux: A Preliminary Take on the New Diagnostic Criteria

Alzheimer’s Redux: A Preliminary Take on the New Diagnostic Criteria

Nearly a year ago, on these pages,1 I expressed concerns regarding a draft report from workgroups at the Alzheimer’s Association International Conference on Alzheimer’s Disease (AAICAD) 2010, which suggested that the term “preclinical Alzheimer’s Disease” might be adopted. At that time, I asked whether “disease” as we ordinarily understand the term can really be “pre-clinical.” I also wondered about the psychological effect of telling an asymptomatic patient, “You have preclinical Alzheimer’s Disease.” Now, 3 expert international workgroups convened by the Alzheimer’s Association and the National Institute on Aging (NIA) have issued the first new criteria and guidelines for diagnosing Alzheimer’s disease in 27 years. The new guidelines appear as free-access papers in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association and are referenced as PDFs, below.

What should we make of these new and very thoughtful guidelines, which are based on the most comprehensive, recent research? A caveat to readers: I have not waded through the voluminous papers referenced, and the following is only my preliminary assessment, based on my reading of the Alzheimer’s Association synopsis.2 According to their press release, 3 phases of Alzheimer’s disease are described by the workgroups, progressing in severity and symptoms:

Preclinical Alzheimer’s Disease. Measurable changes in biomarkers (such as brain imaging and spinal fluid chemistry) indicate the very earliest signs of disease, before outward symptoms are visible. Currently, there are no clinical diagnostic criteria for this phase, but the group provides a scientific framework to help researchers better define this stage.
Mild cognitive impairment (MCI) due to Alzheimer’s Disease. Mild changes in memory and thinking abilities are evident—enough to be noticed and measured—but are not accompanied by impairment that compromises everyday activities and functioning.
Dementia due to Alzheimer’s Disease. Cognitive and behavioral symptoms are present and are of sufficient severity to impair the patient’s ability to function in daily life.

Overall, I applaud the humane intentions of the workgroups, and the carefully nuanced distinctions they have provided. Nonetheless, I am concerned with how clinicians will interpret and use these new guidelines. In my experience, when most patients hear the word, “Alzheimer’s” in reference to their presenting complaints—however carefully the term is qualified—they usually experience intense anxiety, if not panic. Specifically, I remain concerned with the term, “Preclinical Alzheimer’s Disease,” if the term is misused by clinicians. To the credit of the researchers, “The recommendations of the preclinical Alzheimer’s workgroup are intended for research purposes only, and do not have any clinical utility at this time.” But will clinicians faced with patients requesting a PET scan for minimal memory complaints abide by this warning? And if the PET scan is vaguely suggestive of Alzheimer-type pathology, will the clinician tell the patient, “You appear to have preclinical Alzheimer’s Disease”?

Analogies with diagnosing the very earliest, asymptomatic stages of diabetes or hypertension are perfectly understandable from the research and public health perspectives—and the intentions of the researchers are clearly laudable. But these analogies are also somewhat misleading, in that diabetes and hypertension are conditions which, if diagnosed in asymptomatic patients, can be successfully treated in most cases. (Similarly, identifying someone as having a condition on the “softer end” of the bipolar spectrum—whatever the merits and demerits of doing so—entails the possibility of providing useful treatment, such as lithium. At present, this is clearly not the case for persons given the diagnosis “MCI due to Alzheimer’s Disease”).

I also have qualms about the term, “Mild cognitive impairment (MCI) due to Alzheimer’s Disease.” As the synopsis report indicates, “More work is needed to distinguish those with MCI who will go on to develop Alzheimer’s dementia from those who will not.”2 Fair enough—but if, indeed, a percentage of those diagnosed with “MCI due to Alzheimer’s Disease” (with or without a confirming biomarker) will not go on to develop Alzheimer’s Dementia, then in what sense did they have “MCI due to Alzheimer’s Disease”? In retrospect, this designation would amount to a potentially devastating false positive diagnosis. Wouldn’t the diagnosis, “MCI of unclear etiology” be a more conservative and less traumatic diagnosis?

Again, to their credit, the workgroups are sensitive to “. . . the ethical and practical implications” of making a “diagnosis” of Alzheimer’s at a preclinical stage,” and they call for more study of these issues. They specifically raise the question of “why would anyone want to know they have Alzheimer’s a decade before they might develop symptoms, if there is nothing they can do about it?”2 and they urge that this question “. . . be carefully considered well before any results from research [are] translated into clinical practice.”2

I fully agree. After all, our goal as physicians, in the broadest sense, is to reduce the net amount of medically related suffering and misery in the world. If telling patients they have “pre-clinical Alzheimer’s” or “MCI due to Alzheimer’s Disease”—absent effective treatment—produces more emotional suffering than it relieves, a difficult ethical question arises; namely, can such a disclosure be justified under the foundational principle of non-malfeasance?

On the other hand, if empirical studies find that, more often than not, such early disclosure allows patients to lead more fulfilling lives for the time remaining to them—for example, by providing a sense of “closure” or facilitating financial planning—then one might be able to justify such a practice, even absent an effective treatment. This is an empirical question that needs to be studied longitudinally in a large population of patients with very early, preclinical cognitive complaints. Until we have such long-term, prospective data, I would caution clinicians to be exceedingly conservative in applying the term “Alzheimer’s” to any patient who lacks clinically significant degrees of impairment and dysfunction.

In the meantime, let’s hope that the very promising research cited by the workgroups soon leads to an effective treatment for this devastating disease.

For further reading (see National Institute on Aging/Alzheimer’s Association Diagnostic Guidelines for Alzheimer’s Disease from Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association)
Clifford R. Jack Jr., et al. Introduction to the Recommendations from the National Institute on Aging and the Alzheimer’s Association Workgroups on Diagnostic Guidelines for Alzheimer’s Disease.[pdf]

Guy M. McKhann and David S. Knopman, et al. The Diagnosis of Dementia Due to Alzheimer’s Disease: Recommendations from the National Institute on Aging and the Alzheimer’s Association Workgroup.[pdf]

Marilyn S. Albert, et al. The Diagnosis of Mild Cognitive Impairment Due to Alzheimer’s Disease: Recommendations from the National Institute on Aging and Alzheimer’s Association Workgroup.[pdf]

Reisa A. Sperling, et al. Toward Defining the Preclinical Stages of Alzheimer’s Disease: Recommendations from the National Institute on Aging and the Alzheimer’s Association Workgroup.[pdf]



1. Pies R. Alzheimer’s Disease without Dis-ease? New Conundrums for Psychiatric Diagnosis and Public Health. Accessed June 16, 2011.
2. Alzheimer’s Association. New criteria and guidelines for the diagnosis of Alzheimer’s disease published for first time in 27 years. Accessed June 16, 2011.

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